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The deamidases secreted byBurkholderia pseudomalleiandEnteropathogenic Ecolimodify the residue 40 in ubiquitin from a Glutamine (Q) to Glutamate (E), triggering several downstream processes to cause cell cycle arrest and activate immune responses. Deamidation hampers the activity of ubiquitin and its interaction with ubiquitin chain receptors by an unknown mechanism. Here, we study the effect of deamidation on ubiquitin structure and dynamics. We report the crystal structure of the deamidated ubiquitin, supported by NMR and molecular dynamics simulations. The structure reveals a new intra-molecular salt bridge between the deamidated region and the C-terminal tail of ubiquitin. The salt bridge perturbs the dynamics of the ubiquitin tail to reduce affinity for ubiquitin receptors like the p62 ubiquitin-associated domain. The salt bridge disrupts the transition to catalytically active E2~Ub closed conformation. Consequently, RING E3s fail to interact with E2~Ub, reducing ubiquitination activity. Our findings reveal that deamidation-induced intramolecular salt bridges in ubiquitin modulate conformational ensembles to inactivate ubiquitination.

One of the most prevalent gynaecologic malignancies with the greatest fatality rate is ovarian cancer. By recognizing the potential of immune system, immunotherapies have brought about a revolution in the treatment of cancer. However, interactions of malignant, non-malignant, and immune cells in the peritoneal cavity form a unique TME which is less explored in terms of immunosuppression. Less tumour mutational burden and strong immunosuppression in peritoneal TME leads to poor outcome of immune checkpoint inhibition (ICI) and CART cell therapy in ovarian cancer. Therefore, alternative immunotherapeutic strategies are of utmost importance to achieve sound clinical success. The development of peptide vaccines based on tumor-associated antigens (TTAs) displayed in ovarian cancer cells can be a potential target to provoke an anti-tumor immune response and subsequent clearance of tumour cells. This insilico study was conducted to find out potential epitopes for a peptide vaccine construct using the immunopeptidomics landscape of ovarian carcinoma. In this investigation, we have selected MUC16, IDO1, FOLR1, and DDX5 for epitope prediction. Potential epitopes for B-cells, Helper T-lymphocytes (HTL) and Cytotoxic T-lymphocytes (CTL) were predicted on the basis of antigenic, allergenic, and toxic properties to design a multiepitope construct. The insilico evaluation of physicochemical properties and higher order structural analyses of the final construct revealed a potential vaccine candidate. The designed vaccine construct may be employed as a therapeutic immunization candidate for ovarian malignancies either alone or in combination with ICI. However, further in vitro and animal experimentation is required to establish the efficacy of the vaccine candidate.

Background of the study: Students were found to use mobile phone excessively. The pattern of mobile phone use among the students may signal the evolution of mobile phone use from a habit to an addiction.[5] Usage of mobile phones adversely affect student concentration, psychosocial wellbeing and their physiological health which are areas that need attention. The problem is that the use of mobile phone among students has become a habit.[3] Research shows that there is a difference between students’ performance and commitment to academics in lecture rooms from those who use mobile phones during lecture, inattentiveness, and non- participation in academic assignments or field work.[7] Findings of a study indicates that mobile phones play a large part in the daily life of medical student. Therefore, its impact on psychological and health should be discussed among the students to prevent the harmful effects of mobile phones use.[8] Objective of this study is to assess the impact of mobile phone usage on behavior change among undergraduate students and to find out the association between the impact of mobile phone usage on behavior change among undergraduate students with the selected demographic variable. Materials and Methods: Descriptive research design was utilized in this study. Through non discriminative snow ball sampling technique 100 undergraduate students of different disciplines like medical, engineering, agricultural and other science were selected for this study. Self-administered online questionnaire was used to gather the data from the participants. Descriptive and inferential statistics was used to analyze the data. Results: impact of mobile phones among 1% of undergraduate students is mild, 94% of undergraduate students had moderate impact and remaining 5% of them reported that the impact of mobile phone on their human behavior is severe. The overall mean impact score was 91.21 and obtained SD was 22.34. Conclusion: Results of this study shows that the usage of mobile phone has moderate to severe impact among the behavior of the undergraduate students. Though the need of mobile phone is inevitable there needs have to be balanced between time spent with these devices, and without them. Without a set balance, people will continue to become more obsessed and consumed by technology, and there is a concern that humans will lose all closeness and affection that can come from personalized conversations.

Gaucher disease is a genetic disorder and the most common lysosomal disease caused by the deficiency of enzyme β-glucocerebrosidase (GCase). Although enzyme replacement therapy (ERT) is successfully applied using mannose-exposed conjugated glucocerebrosidase, the lower stability of the enzyme in blood demands periodic intravenous administration that adds to the high cost of treatment. In this work, the enzyme β-glucocerebrosidase was encapsulated inside virus-like nanoparticles (VLPs) from brome mosaic virus (BMV), and their surface was functionalized with mannose groups for targeting to macrophages. The VLP nanoreactors showed significant GCase catalytic activity. Moreover, the Michaelis-Menten constants for the free GCase enzyme (K

Multi-mode bioimaging using a combination of two or more imaging techniques is beneficial for taking advantage of each modality by overcoming the individual limitations. It allows visualization of ...

Chalcone derivatives have been successfully utilized for a range of biological applications and can cross the blood-brain barrier easily. β-amyloid-specific bis-chalcone derivative, 6,9-bis(carboxymethyl)-14-(4-[(E)-3-(4-(dimethylamino)phenyl)acryloyl]phenoxy)-3-(2-[(2-(4-[(E)-3-(4-(dimethylamino)phenyl)acryloyl]phenoxy)ethyl)amino]-2-oxoethyl)-11-oxo-3,6,9,12-tetraazatetradecanoic acid, DT(Ch)

A Corn is a specially-shaped callus of dead skin that occurs on the thin or glabrous surface of the toe. It presses upon the adjacent tissues and causes severe pain when pressed due to pressure on the nerves. Plantar corns are recalcitrant to the medical line of treatment and being very painful need surgical intervention. Surgery is rarely indicated since the rate of recurrences is as high as with conservative therapy The management of Kadara is aimed at the removal of the hyperkeratosis lesion by Snigdha Agni Karma along with Shastra Karma. Here, we demonstrated an OPD base simple and effective ancient technique in corns as described in Samhita which found to be very beneficial.

The current photodynamic therapy (PDT) is majorly hindered by the shallow penetration depth and oxygen dependency, limiting its application to deep-seated solid hypoxic tumors. Thus, it is meaningful to develop efficient X-ray mediated PDT system capable of generating reactive oxygen species (ROS) under both the normoxic and hypoxic conditions. Herein, we report the synthesis and characterization of nanocomposite, YAG:Pr@ZnO@PpIX with an amalgamation of UV-emitting Y2.99Pr0.01Al5O12 (YAG:Pr) nanoscintillator, and zinc oxide (ZnO) and protoporphyrin IX (PpIX) as photosensitizers. YAG:Pr surface was coated with a ZnO layer (∼10 nm) by atomic layer deposition, and then PpIX was covalently conjugated via a linker to give YAG:Pr@ZnO@PpIX. The photo- and cathodoluminescence analyses gave the evidences of efficient energy transfer from YAG:Pr to ZnO at ∼320 nm, and YAG:Pr@ZnO to PpIX at Soret region (350–450 nm). The nanohybrid was able to produce both, Type I and Type II ROS upon direct and indirect photoactivation with UV365nm and UV290nm, respectively. In vitro cytotoxicity of non-activated YAG:Pr@ZnO@PpIX in mouse melanoma cells revealed low toxicity, which significantly enhanced upon photoactivation with UV365nm indicating the photokilling property of the nanohybrid. Overall, our preliminary studies successfully demonstrate the potential of YAG:Pr@ZnO@PpIX to overcome the limited penetration and oxygen-dependency of traditional PDT.

The one-pot cascade reaction of naturally occurring enzymes is exciting for highly selective complex reaction and biodegradable approaches. Tamoxifen is the main drug against breast cancer for decades and induces an anticancerous effect upon metabolic activation by cytochrome P450 (CYP450). Herein, bi-enzymatic nanoreactors (NRs) are developed as a multimodality platform for smart action against breast tumors. CYPBM3 of Bacillus magaterium (CYP) is co-confined with glucose oxidase (GOx) where GOx produces H2O2 in the presence of glucose that elicits the CYP-mediated transformation of tamoxifen. The scintillating and mesoporous LaF3:Tb as nanocarrier showed advantages like a wide range of pore size and positive surface charge for efficient loading of enzyme couple, while the smallest pores were available for substrate/product diffusion. The obtained NRs were camouflaged with human serum albumin (HSA) to overcome premature enzyme leaching and provide active stealth properties. The nanocomposite was characterized for physicochemical properties and glucose-mediated sequential catalysis. The in vitro studies demonstrated the cell internalization of NRs in both ER+ and triple-negative breast cancer cell lines and showed significant cytotoxicity. The developed NRs not only improve the outcomes of endocrine therapy in ER+ cells but also synergistically act with oxidation therapy for enhanced therapeutic effect. Importantly, inhibition of triple-negative cells was also achieved. Thus, the development of the new multimodal nanomedicine of the present work should afford new tools towards the theranosis of breast cancer with minimized adverse effects.

The paper addresses the possibility of leveraging a microservices-based paradigm to leverage blockchain technology in the emergent programmable distributed infrastructure for 5G and future networks. Different use-cases such as user data privacy management, healthcare emergency services, or edge information delivery, and for emerging 5G use-cases leveraging such distributed blockchain infrastructure are considered. In particular, for data privacy related management, a separation of the control plane and the user/data plane is considered to record blockchain transaction data in the control plane, while recording a hash associated with the transaction in the user/data plane. The paper also discusses possible future extensions in emerging future networks.

Homodimeric chalcone based 11C-PET radiotracer, 11C-(Chal)2DEA-Me, was synthesized, and binding affinity toward beta amyloid (Aβ) was evaluated. The computational studies revealed multiple binding of the tracer at the recognition sites of Aβ fibrils. The bivalent ligand 11C-(Chal)2DEA-Me displayed higher binding affinity compared to the corresponding monomer, 11C-Chal-Me, and classical Aβ agents. The radiolabeling yield with carbon-11 was 40–55% (decay corrected) with specific activity of 65–90 GBq/μmol. A significant (p 93% intact tracer at 30 min po...

Fouling on the gas-exchange hollow-fiber membrane (HFM) of extracorporeal membrane oxygenation (ECMO) devices by blood components and pathogens represents the major hurdle to their long-term application in patients with lung deficiency or unstable hemodynamics. Although patients are treated with anticoagulants, deposition of blood proteins onto the membrane surface may still occur after few days, leading to insufficient gas transfer and, consequently, to device failure. The aim of this study was to establish an endothelial cell (EC) monolayer onto the gas-exchange membrane of an ECMO device with a view to developing a hemocompatible bioartificial lung. Poly(4-methyl-1-pentene) (PMP) gas-exchange membranes were coated with titanium dioxide (TiO2), using the pulsed vacuum cathodic arc plasma deposition (PVCAPD) technique, in order to generate a stable interlayer, enabling cell adhesion onto the strongly hydrophobic PMP membrane. The TiO2 coating reduced the oxygen transfer rate (OTR) of the membrane by 22%, and it successfully mediated EC attachment. The adhered ECs formed a confluent monolayer, which retained a non-thrombogenic state and showed cell-to-cell, as well as cell-to-substrate contacts. The established monolayer was able to withstand physiological shear stress and possessed a “self-healing” capacity at areas of induced monolayer disruption. The study demonstrated that the TiO2 coating mediated EC attachment and the establishment of a functional EC monolayer. Statement of Significance Surface endothelialization is considered an effective approach to achieve complete hamocompatibility of blood-contacting devices. Several strategies to enable endothelial cell adhesion onto stents and vascular prostheses have already been described in the literature. However, only few studies investigated the feasibility of establishing an endothelial monolayer onto the gas exchange membrane of ECMO devices, using peptides or proteins that were weakly adsorbed via dip coating techniques. This study demonstrated the effectiveness of an alternative and stable titanium dioxide coating for gas-exchange membranes, which enabled the establishment of a confluent, functional and non-activated endothelial monolayer, while maintaining oxygen permeability.

Endocrine disruptor compounds (EDCs) are pollutants able to alter both hormone synthesis and their regulation in animals and humans, thus, EDCs represent a risk for public health and for the environment. Cytochrome P450 enzymes (CYPs) are involved in the detoxification of a wide range of compounds, and it has been established that these enzymes produce the initial biotransformation of many EDCs. In this work, a bionanoreactor based on the encapsulation of an enhanced peroxygenase CYPBM321B3 inside the capsid of bacteriophage P22 virus-like particles (VLPs) was designed and characterized. VLPs were functionalized with glucose oxidase to generate in situ hydrogen peroxide necessary to activate the transformation of bisphenol A, nonylphenol, 17β-estradiol, triclosan, and resorcinol. Catalytic parameters, as well as the chemical nature of reaction products are presented. The enzymatic nanoreactors showed specific activities varying from 0.175 to 0.456 min−1 in the transformation of these EDCs, which are equivalent to 22–77% of the activity obtained with free CYP. The capacity to transform structurally diverse compounds, easy production and glucose fueled catalytic activity make these enzymatic nanoreactors an interesting platform for enzyme delivery in the biomedical field.

Background: Caudal analgesia reduces the amount of inhaled and intravenous (i.v.) anaesthetic requirement, attenuates the stress response to surgery, facilitates a rapid, smooth recovery and provides good post operative analgesia and sedation. Methods: 135 patients of either sex, aged between 2 to 8 years, having body weight 10 to 30kg belonging to ASA Grade I and II scheduled for infraumblical surgeries under GA were randomized into three groups of 45 each to receive the caudal block i.e Group A received .25% levobupivacaine (.75ml/kg) with 0.9%NS. Group B received .25%levobupivacaine (.75ml/kg) with fentanyl 1mcg/kg diluted with 0.9%NS upto 1ml and Group C received 0.25%levobupivacaine (0.75ml/kg) with dexmedetomidine 1mcg/kg diluted with 0.9%NS upto 1ml. Results: There was statistically insignificant difference in the socio- demographic variables in terms of age, weight, sex ratio, ASA Grade and duration of surgery among the study groups. There was statistically significant (p

This paper discusses the design of a mobile number portability processing system in the telecom domain with a solution proposed using permissioned private blockchain technology. As a first step, the system is designed to be managed by a neutral entity. Subsequently, the design is extended to be supported by a neutral blockchain-based platform. The Hyperledger Fabric blockchain platform is used as the framework to develop the solution. Channels are utilized for different subsets of nodes that interact with each other to enable transactions in the system. Concurrent state transition graph paths are utilized to enable faster processing in the blockchain system. The paper concludes with experimental results and possibilities for future extensions.

Phosphonates-based agents are well-known bone-seeking radiopharmaceuticals with application in detection and therapy. With higher sensitivity and resolution offered by Positron Emission Tomography (PET), tracers based on this technique are gaining huge attention. 68Ga-based generator and radiotracers render independence from the on-site cyclotron. We report the development of 68Ga-labeled DOTA-based bismacrocyclic phosphonate derivative, for bone PET imaging. The synthesis and characterization of 68Ga- DO3P-AME-DO3P was carried out in > 95% purity. The radiotracer displayed high stability and low binding affinity (

Synthetic indigo is among the most important industrial dyes. Unfortunately, synthetic indigo has raised environmental concern due to the use of pollutant and hazardous chemicals. In response, green chemistry aims to find new environmentally friendly and economically attractive synthesis methods. Accordingly, this work describes the enzymatic synthesis of indigo and its derivatives starting from indole. A variant of the heme domain of cytochrome P450 from Bacillus megaterium, CYPBM3F87A, was used to catalyze the synthesis of indigo and three di-substituted derivatives. Substrates transformed by a peroxygenase reaction were indole, 4-bromoindole, 5-methoxyindole and 7-methoxyindole. The kinetic data fitted to Hill's mathematical model with kcat values of 3.51, 0.94, 4.72, and 4.28 min−1 for each substrate, respectively. In all cases, colored products were obtained that were characterized by spectrometric techniques. Furthermore, the CYPBM3F87A enzyme was immobilized on magnetic nanoparticles that exhibited catalytic rate in the synthesis of indigo from indole (kcat 0.72 min−1). Our results show that enzymatic synthesis of industrial dyes without the use of expensive cofactors offers an attractive and plausible alternative to conventional chemical synthesis with a lower environment impact.

Background: Intraocular pressure (IOP) is increased during laparoscopic surgery with Trendelenburg position and may contribute to deleterious effects on optic nerve in susceptible patients. Aims: The primary objective of this study is to compare the effects of propofol-based total intravenous anesthesia (TIVA) with those of sevoflurane anesthesia on IOP in patients undergoing lower abdominal laparoscopic surgery in Trendelenburg position. Secondary objectives are to compare hemodynamic changes, mean arterial pressure (MAP), end-tidal CO2, and peak inspiratory pressure changes. Materials and Methods: Sixty patients with physical status American Society of Anesthesiologists classes I and II were randomly allocated in two groups: Group A (propofol) and Group B (sevoflurane). IOP along with other parameters was measured at seven points including baseline (T0), 5 min after induction (T1), 5 min after CO2 pneumoperitoneum in supine position (T2), 30 min after CO2 pneumoperitoneum with Trendelenburg position (T3), 5 min after returning to supine position (T4), 5 min after CO2 desufflation (T5), and 5 min after extubation (T6). Results: The change in IOP was different between the two groups. Maximum rise in IOP was seen at T3, and mean ± standard deviation IOP was 15.5 ± 0.9 mmHg and 19.8 ± 1.2 mmHg in Group A and Group B, respectively (P < 0.01). In Group A (propofol), IOP remained almost equal to the baseline value at T3 and the IOP difference was 0.3 ± 0.9 mmHg less than baseline (statistically insignificant, P > 0.05), while in Group B (sevoflurane), IOP increased significantly at T3 and the difference was 4.0 ± 1.2 mmHg (P < 0.001). The IOP was significantly greater (P < 0.01) from T2 to T6 in sevoflurane group than propofol group. Conclusion: Propofol-based TIVA is more effective than inhalational anesthesia with sevoflurane in attenuating the increase in IOP during laparoscopic surgery requiring CO2 pneumoperitoneum with Trendelenburg position.

Homodimeric chalcone based

Background Tamoxifen is the standard endocrine therapy for breast cancers, which require metabolic activation by cytochrome P450 enzymes (CYP). However, the lower and variable concentrations of CYP activity at the tumor remain major bottlenecks for the efficient treatment, causing severe side-effects. Combination nanotherapy has gained much recent attention for cancer treatment as it reduces the drug-associated toxicity without affecting the therapeutic response. Results Here we show the modular design of P22 bacteriophage virus-like particles for nanoscale integration of virus-driven enzyme prodrug therapy and photodynamic therapy. These virus capsids carrying CYP activity at the core are decorated with photosensitizer and targeting moiety at the surface for effective combinatory treatment. The estradiol-functionalized nanoparticles are recognized and internalized into ER+ breast tumor cells increasing the intracellular CYP activity and showing the ability to produce reactive oxygen species (ROS) upon UV365 nm irradiation. The generated ROS in synergy with enzymatic activity drastically enhanced the tamoxifen sensitivity in vitro, strongly inhibiting tumor cells. Conclusions This work clearly demonstrated that the targeted combinatory treatment using multifunctional biocatalytic P22 represents the effective nanotherapeutics for ER+ breast cancer. Electronic supplementary material The online version of this article (10.1186/s12951-018-0345-2) contains supplementary material, which is available to authorized users.

Calcium concentration modulation both inside and outside cell is of considerable interest for nervous system function in normal and pathological conditions. MRI has potential for very high spatial resolution at molecular/cellular level. Design, synthesis and evaluation of Gd-DO3A-AME-NPHE, a calcium responsive MRI contrast agent is presented. The probe is comprised of a Gd(3+)-DO3A core coupled to iminoacetate coordinating groups for calcium induced relaxivity switching. In the absence of Ca(2+) ions, inner sphere water binding to the Gd-DO3A-AME-NPHE is restricted with longitudinal relaxivity, r1 = 4.37 mM(-1) s(-1) at 4.7 T. However, addition of Ca(2+) triggers a marked enhancement in r1 = 6.99 mM(-1) s(-1) at 4.7 T (60% increase). The construct is highly selective for Ca(2+) over competitive metal ions at extracellular concentration. The r1 is modulated by changes in the hydration number (0.2 to 1.05), which was confirmed by luminescence emission lifetimes of the analogous Eu(3+) complex. T1 phantom images establish the capability of complex of visualizing changes in [Ca(2+)] by MRI.

An anthraquinone conjugated macrocyclic chelating agent, 2,2',2″-(10-(2-(9,10-dioxo-9,10-dihydroanthracen-1-ylamino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid or DO3A-Act-AQ, was synthesized by reacting trisubstituted cyclen (DO3A) with 2-chloro-N-(9,10-dioxo-9,10-dihydro-anthracen-1-yl)-acetamide and radiolabeled with (68)GaCl3 in 84% efficiency and a specific activity of 4.62 MBq/nmol. The IC50 value for BMG-1 cells was 0.1 mM, while the same concentration of DO3A-Act-AQ rendered no significant toxicity in HEK cells. The exposure of BMG-1 cells with 0.1 mM DO3A-Act-AQ displayed a time-dependent increase in apoptosis (40.7% at 4 h and 53% at 24 h), and the effect was 2.8- and 3.6-fold % higher as seen in HEK cells. An increase in S-phase cell population suggested S-phase arrest concomitant with induction of apoptosis in BMG-1 cells reaching to 4.5 times after 24 h with respect to control cells. DNA binding studies on CT-DNA (calf thymus) revealed a quenching pattern in the presence of DO3A-Act-AQ (10-70 μM), and the Stern-Volmer quenching constant was 2.4157 × 10(6) L mol(-1), indicative of strong binding with ds-DNA. A decrease in the positive and negative bands of CT-DNA was seen at 278 nm and 240 nm, respectively, on addition of 0.05 mM of DO3A-Act-AQ in CD studies. (68)Ga-DO3A-Act-AQ was stable in vitro in both PBS and human serum for at least 2 h. The in vivo blood kinetics study performed on normal rabbits indicated fast clearance with t1/2(F) = 40 ± 0.3 min and t1/2(S) = 3 h 30 min ± 0.1 min. Ex vivo biodistribution analysis displayed a favorable tumor-to-muscle ratio of 8.4 after 2 h in athymic nude mice xenografted with BMG-1 cells, suggesting the specificity of (68)Ga-DO3A-Act-AQ toward tumors.

The synthesis of estradiol based bivalent ligand [(EST)2DT] is reported and its potential for targeted imaging and therapy of ER(+) tumors has been evaluated. For the purpose, ethinylestradiol was functionalized with an azidoethylamine moiety via click chemistry. The resultant derivative was reacted in a bivalent mode with DTPA-dianhydride to form the multicoordinate chelating agent, (EST)2DT which displayed capability to bind (99m)Tc. The radiolabeled complex, (99m)Tc-(EST)2DT was obtained in99% radiochemical purity and 20-48 GBq/μmol of specific activity. RBA assay revealed ∼15% binding with estrogen receptor. Evaluation of ligand on ER(+)-cell line (MCF-7) suggested enhanced and ER-mediated uptake. In vivo assays displayed early tracer accumulation in MCF-7 xenografts with tumor to muscle ratio ∼6 in 2 h and negligible uptakes in nontargeted organs. MTT assay performed on ER(+) and ER(-) cell lines displayed selective inhibition of ER(+) cancer cell growth with IC50 = 14.3 μM which was comparable to tamoxifen. The anticancer activity of the ligand is possibly due to the increase in ERβ and suppression of ERα protein levels in gene transcription. The studies reveal the potential of (EST)2DT as diagnostic imaging agent with the additional benefits in therapy.

The impact of exclusion of solar UV-B (280–320 nm) and UV-A+B (280–400 nm) radiation on the root nodules was studied in soybean(Glycine max var. MACS 330). Soybean plants were grown in the tropical region of Indore (Latitude-22.4°N), India under field conditions in metal cages covered with polyester exclusion filters that specifically cut off UV-B (

Background: Although the advantages of ventilation with i-gel™ and laryngeal mask airway Supreme (LMA-Supreme™) has been well documented, they are still under debate for surgeries requiring flexion and extension of neck such as thyroid surgery, tonsillectomy, and neck exploration. Hence, we conducted a study to demonstrate the effect of neck flexion and extension in spontaneously breathing anesthetized pediatric patients utilizing i-gel™ and LMA-Supreme™. Methods: A prospective, randomized comparative study was conducted on sixty children, thirty each in i-gel™ and LMA-Supreme™ group. Oropharyngeal leak pressure (OPLP), fiberoptic view of vocal cords, and exhaled tidal volume were evaluated in neutral, flexion, and extension neck positions in spontaneously breathing children. Results: OPLP for i-gel™ was found to be significantly higher in flexion (29.00 ± 1.95 cmH2O, P < 0.001) and lower in extension (21.07 ± 2.08 cmH2O, P < 0.001) as compared to neutral (24.67 ± 2.08 cmH2O). Similar results were observed for LMA-Supreme™ which showed significantly higher OPLP in flexion (24.73 ± 2.26, P < 0.001 respectively) and lower in extension (18.67 ± 1.42 cmH2O, P < 0.001) as compared to neutral (20.87 ± 1.80 cmH2O). Worsening of fiberoptic view occurs for i-gel™ and LMA-Supreme™ in flexion (10/12/5/3/0 and 11/14/2/2/1, P < 0.05) as compared to neutral position (17/10/2/1/0 and 15/12/1/1/1), respectively. Significant change did not occur in extension. Ventilation worsening occurred in flexion as compared to neutral position evidenced by significant decrease in exhaled tidal volume (92.90 ± 11.42 and 94.13 ± 7.75 ml, P < 0.05) as compared to neutral (100.23 ± 12.31 and 101.50 ± 8.26 ml) for i-gel™ and LMA-Supreme™, respectively. Conclusion: Neck flexion caused a significant increase in leak pressure in both i-gel™ and LMA-Supreme™. With deterioration of fiberoptic view and ventilation, both devices should be used cautiously in pediatric patients in extreme flexion.

Classic hemophilia or hemophilia A is a congenital bleeding diathesis in which the affected individual may present with spontaneous hemorrhage or persistent bleeding even after minor trauma. Knowledge about the disease process, multidisciplinary team approach, and timely management can lead to favorable outcome in these patients. We report management of a child with hemophilia A for suturing of lacerated upper lip mucosa following trauma. A review of literature with recommendations for perioperative management, especially in the setting of emergency surgery, is also provided.

La enfermedad de Gaucher es un trastorno metabólico y el más común entre las enfermedades de almacenamiento lisosomal, es causado por la deficiencia en la actividad de la enzima glucocerebrosidasa (Gcase). La ausencia de la actividad enzimática de la glucocerebrosidasa origina la acumulación del sustrato glucocerebrósido en los macrófagos. Esta acumulación ocasiona hepatomegalia, esplenomegalia, anemia, trombocitopenia entre otras complicaciones. Los pacientes con esta enfermedad se someten a tratamientos que consisten en la administración vía intravenosa de la glucocerebrosidasa exógena diseñada para ser reconocida por los receptores de manosa en los macrófagos. Sin embargo, a pesar del éxito de la terapia de reemplazo enzimático (ERT), la enzima Gcase carece de estabilidad en sangre y a esto se le suma el alto costo de las infusiones necesarias de la enzima al organismo por lo que se ve limitado el tratamiento. Para superar estas limitaciones, en este proyecto se encapsidó la enzima glucocerebrosidasa en nanopartículas tipo virus (virus-like particles, VLPs) y se funcionalizó su superficie con grupos de manosa para ser dirigidos a los macrófagos. Bajo un análisis de la actividad enzimática, las constantes de Michaelis-Menten para la enzima Gcase libre (KM = 2.20 mM) y la enzima encapsidada en las VLPs (KM = 2.23 mM) fueron similares. La enzima en las VLPs mostró el 78.9% de la actividad catalítica en comparación con la enzima Gcase libre. Es importante destacar que la estabilidad de la enzima Gcase en condiciones fisiológicas (pH 7.4, 37°C) se mejoró en  15 veces después de la encapsidación, lo que es beneficioso para obtener una vida media de circulación sanguínea más alta de la enzima Gcase, lo que puede reducir el costo de la terapia al disminuir el número de inyecciones intravenosas. Finalmente, los nanorreactores con actividad enzimática β-glucocerebrosidasa se sintetizaron y caracterizaron con éxito. El análisis preliminar sugiere el potencial de estos nanorreactores en la ERT de la enfermedad de Gaucher. Gaucher disease is a genetic disorder and the most common lysosomal disease caused by the deficiency of enzyme glucocerebrosidase. This results in the accumulation of glucosylceramide in lysosomes of macrophages cell. It leads to hepatomegaly, splenomegaly, anemia, thrombocytopenia, among other complications. Although enzyme replacement therapy (ERT) is successfully applied using mannose conjugated glucocerebrosidase, the lower stability of the enzyme in blood demands periodically intravenous administration that adds to the high cost of the treatment. Moreover, immunogenicity is also a concern. In this work, the enzyme glucocerebrosidase was encapsulated inside virus-like nanoparticles (VLPs), and their surface was functionalized with mannose groups to be targeted to macrophages. The VLPs of brome mosaic virus (BMV) were used for encapsulation of enzymes. Under an analysis of the enzymatic activity, the Michaelis-Menten constants for the free Gcase enzyme (KM = 2.20 mM) and the enzyme encapsidated in the VLPs (KM = 2.23 mM) were similar. The enzyme in the VLPs showed 78.9% of the catalytic activity compared to the free Gcase enzyme. Importantly, the stability of enzymes under physiological conditions (pH 7.4, 37 ˚C) was enhanced by  15-fold after encapsulation that is beneficial for obtaining higher blood circulation half-life, which may reduce the cost of therapy by reducing the requirement of multiple intravenous injections. Finally, the nanoreactors with enzymatic activity β-glucocerebrosidase were successfully synthesized and characterized. The preliminary analysis suggests the potential of these nanoreactors in ERT of Gaucher’s disease.